Our investigations continue to be directed toward two major objectives: 1) identification of individuals at risk for sudden death; and 2) development of therapeutic measures for protecting against lethal cardiac arrhythmias. The essential hypothesis guiding our work is that ventricular fibrillation is provoked by transient risk factors which act upon the electrically unstable myocardium. These risk factors derive primarily from altered central nervous system activity. These risk factors derive primarily from altered central nervous system activity. Specifically, our goals are: 1) to develop noninvasive techniques for assessing cardiac electrical instability in the conscious animal; 2) to further investgate the electrophysiologic basis of the protective zone; 3) to determine the effect of new antiarrhythmic drugs during both myocardial ischemia and reperfusion; 4) to explore the possibility of protecting against ventricular fibrillation using agents which act on the central nervous system. In the area of human studies, we plan to continue the development of methodologies to expose ventricular arrhythmias and thus assist in the determination of antiarrhythmic drug efficacy. The continued use of investigational drugs in the management of ventricular arrhythmias will occupy a substantial portion of clinical time.